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<p>Ischemic stroke (IS) accounts for approximately 70% of global stroke cases and remains a leading cause of mortality and disability due to the limitations of conventional drug delivery systems in overcoming the blood-brain barrier (BBB). This study presents an innovative nanotechnology-based intranasal drug delivery system utilizing aminated chitosan (AmCs) nanoparticles encapsulating thymoquinone (TQ), a bioactive neuroprotective compound. The optimized TQ-AmCs nanoparticle formulation exhibited a particle size of 135.9&#xa0;nm, an entrapment efficiency of 87.75%, and a sustained drug release of 88.46% over 24&#xa0;h. Pharmacokinetic studies demonstrated a 75.21% drug targeting efficiency index (DTI) and a 2.5-fold increase in bioavailability compared to conventional formulations. Ex vivo studies confirmed a 1.5-fold enhancement in nasal mucosa permeability, ensuring efficient nose-to-brain delivery. Brain pharmacokinetic analysis further revealed significantly higher Cmax (41.61&#xa0;µg/mL), AUC (49.87&#xa0;µg h/mL), and mean residence time (MRT) (26.87&#xa0;h) for intranasally administered TQ-AmCs nanoparticles compared to traditional formulations. These findings, supported by extensive in vitro, ex vivo, and in vivo studies, underscore the potential of nanotechnology-enhanced intranasal drug delivery as a transformative approach for ischemic stroke therapy, offering superior brain-targeting efficiency and prolonged neuroprotection.</p> Graphical Abstract <p></p>

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Nanoparticle-Enhanced Intranasal Drug Delivery: A Novel Strategy for Efficient Brain Targeting in Ischemic Stroke

  • 期刊论文

  • 发表日期：

    2025年11月17日

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  • Guruprasad P. Khanapure,
  • Minal V. Bhanje,
  • Ujban Hussain,
  • Mohammed Qutub,
  • Samiksha Tammewar,
  • Veena Belgamwar,
  • Amol A. Tatode

摘要

Ischemic stroke (IS) accounts for approximately 70% of global stroke cases and remains a leading cause of mortality and disability due to the limitations of conventional drug delivery systems in overcoming the blood-brain barrier (BBB). This study presents an innovative nanotechnology-based intranasal drug delivery system utilizing aminated chitosan (AmCs) nanoparticles encapsulating thymoquinone (TQ), a bioactive neuroprotective compound. The optimized TQ-AmCs nanoparticle formulation exhibited a particle size of 135.9 nm, an entrapment efficiency of 87.75%, and a sustained drug release of 88.46% over 24 h. Pharmacokinetic studies demonstrated a 75.21% drug targeting efficiency index (DTI) and a 2.5-fold increase in bioavailability compared to conventional formulations. Ex vivo studies confirmed a 1.5-fold enhancement in nasal mucosa permeability, ensuring efficient nose-to-brain delivery. Brain pharmacokinetic analysis further revealed significantly higher Cmax (41.61 µg/mL), AUC (49.87 µg h/mL), and mean residence time (MRT) (26.87 h) for intranasally administered TQ-AmCs nanoparticles compared to traditional formulations. These findings, supported by extensive in vitro, ex vivo, and in vivo studies, underscore the potential of nanotechnology-enhanced intranasal drug delivery as a transformative approach for ischemic stroke therapy, offering superior brain-targeting efficiency and prolonged neuroprotection.

Graphical Abstract